We propose to develop an animal model and a tissue culture model for the study of the treatment of human arginase deficiency by enzyme replacement. Arginase is distinguished from other enzymes for which replacement therapy is being intensively studied by its location outside of the lysosome. Bovine arginase will be purified and administered to rabbits. The endogenous enzyme will be distinguished from that of the host by specific immunoprecipitation with rabbit anti-rat liver arginase antibody. The enzyme will be administered by direct infusion, by encapsulation in red blood cell ghosts, by immobilization on solid support and eventually in liposomes. The rate of disappearance of enzyme from the circulation; the organ, cellular, and subcellular distribution of the enzyme; the half-life of the enzyme in various compartments; and the effectiveness of the enzyme in the hydrolysis of endogenous or exogenous arginine will be assessed. The uptake of arginase encapsulated in liposomes into the cytoplasm will be studied in several cell culture systems and the effect of fusogenic protein purified from Sendai virus on the efficiency of this process will be measured.